This is a Program Project Grant on human malignant gliomas and medulloblastoma. As detailed in the body of this application, these two nervous system neoplasms remain as significant health problems. Despite intensive research efforts by many investigators, there has been little progress made in the etiology, early diagnosis, or treatment of malignant primary brain tumors during the last 20 years. This Program Project Grant will solidify and intensify the efforts of an outstanding group of internationally recognized investigators with a long history of effective collaboration. They will approach the malignant brain tumor problem in areas of etiology, diagnosis, pre-clinical, and clinical treatment. Projects range from mechanistic studies on promotion and progression of brain tumors in experimental animals (Project 4) to development and characterization of operationally specific glioma antigens defined my murine and primate monoclonal antibodies (Project 1); analysis and manipulation of control of blood flow and permeability in gliomas and medulloblastoma (Project 2); new methods of treatment of brain tumors in experimental animal with antigenic modification of tumor cells and utilization of specialized drug and radiation delivery systems (Project 3); and clinical investigation (Project 5), extending an immunotherapeutic trial which has been shown non-toxic and highly promising in phase I trials and initiating a randomized phase III evaluation of a new drup (AZQ) which has been show to be highly promising phase II trials.